Nonketotic hyperglycinemia

Brief introduction
High glycine Hyperlipidemia refers to body fluids of glycine (glycine) high concentration of disease, high glycine has two kinds: non-ketone and ketone sexual. Non-keto high pathogenicity of glycine hyperlipidemia are the main mechanism to split the system because glycine (glycine cleavage system, GCS) of the defect caused by the degradation of glycine. High non-ketone is a glycine Hyperlipemia occur during the neonatal period and there is a very serious biochemical metabolic abnormalities. Another one of the high glycine hyperlipidemia (ketotic hyperglycinemia) is the most lethal symptoms of ketoacidosis are mainly because of organic acid disorders are a result of ketoacidosis and high glycine hyperlipidemia, and such diseases are usually happen early in life.


Clinical symptoms

Non-keto high glycine Hyperlipemia clinical characterization can be divided into two types: type newborn (neonatal type) and late onset (late-onset type).

Newborns are more common type, the majority of cases of this type is quite normal at birth, but shortly after, usually little more than 48 hours, neurological symptoms will appear and the rapid deterioration of the muscles such as low-tension (muscle hypotonic), the Moro Test low response (depressed Moro response), epilepsy (seizure), asphyxia (apnea attack), sleepiness (lethargy) or unconscious (coma). Most of the cases will be dead in a few weeks, after this period of time while still alive there is a serious developmental delay mental exercise phenomenon. In addition, there is also likely to attack various types of cramps, myoclonic epilepsy from the onset of epilepsy Tai may have happened, have hiccups situation is also very common. Neonatal period there will be very clear with low muscle tension, and then will gradually become stiff muscles.

Late onset cases in the neonatal period will not have abnormal symptoms, and then will be gradually developed various degrees of neurological symptoms, their age of onset ranging from infancy to adolescence.




Metabolic degradation

Non-keto high defect Hyperlipemia glycine at glycine are split system (GCS), glycine split system is a multi-enzyme system by combination of four proteins: P protein (a pyridosal phosphate-dependant glycine decarboxylase), H protein (a lipoic acid-containing protein), T protein (a tetrahydrofolate-requiring enzyme), and L-protein (lipoamide dehydrogenase). In 30 newborns in the liver of patients who measured the activity of glycine-free or very low, whereas in late onset cases are detected only residual activity, so from the severity of clinical symptoms of view also seems to glycine split system the degree of defect.


Non-keto high hyperlipidemia cases glycine glycine concentration in the brain than one high glycine high hyperlipidemia cases; and non-keto high hyperlipidemia cases glycine glycine brain activity is to split the system Measuring less than one high and hyperlipidemia glycine glycine case of split brain system showed normal activity.


Most of the non-ketone high glycine hyperlipidemia are sick belong to P protein has defects, a small number of proteins for the T defect. Seven patients from the brain and the liver anatomical analysis of that brain and liver glycine split protein system is controlled by the same gene.

Recently, a lot of study and observation of the brain glycine exciting link between agents and some new views. Before glycine has been regarded as a nerve conduction inhibitor, but now it is found that while there is some role in nerve excitability, and high concentrations of glycine on the developing brain damage.

Diagnostic tests


Happen when the baby epilepsy, low muscle tension, and drowsiness when these symptoms are not from infection, trauma, hypoxia, or other common pediatric problem, should be strongly suspected at this time whether the patient is suffering from congenital metabolic diseases. At this point the patient should be analyzed in blood amino acids and urine organic acids, as found in abnormal blood glycine increased, we should then consider the possibility of the disease, the disease takes and one high glycine Hyperlipemia make one distinction. The disease generally have normal blood pH and normal organic acid test results (which may be gas-phase analyzer layer inspection to determine the urine). Second, comparable brain fluid and plasma glycine concentrations, the ratio is as follows:



1. Cerebrospinal fluid of glycine: glycine in plasma of> 0.09 = non-ketone high glycine Hyperlipemia



2. Cerebrospinal fluid of glycine: glycine in plasma of <0.09 and> 0.04 = normal



3. Cerebrospinal fluid glycine: plasma glycine <0.04 = one of the high glycine hyperlipidemia.



Since glycine split systems are present in liver, kidney, and brain, liver anatomy therefore contribute to high non-ketone glycine enzyme diagnosis of hyperlipidemia.



Prenatal genetic diagnosis


Since the current non-ketone high glycine Hyperlipemia no effective method of treatment, so prenatal diagnosis is very necessary. Cultured amniotic fluid cells, glycine-free split system activity and therefore does not apply to prenatal genetic diagnosis, but glycine decomposition of the system exist in the villous placenta, so human chorionic sampling applied to make the non-ketone high glycine Prenatal genetic diagnosis of hyperlipidemia. Moreover, if the family's gene mutation point has been identified, and the gene (DNA) diagnosis is feasible.



Treatment and clinical progress


Patients in order to reduce the concentration of glycine, clinical reports on the use has been a lot of treatment methods including the restriction of the protein diet, this diet is the non-glycine and its precursors serine (serine); use of benzoic acid salt (Benzoate) combined hippuric acid glycine become discharged by the kidneys; injection ursodeoxycholic acid glycine to link out from the bile excretion. These treatments can effectively reduce the plasma concentrations of glycine can not effectively reduce the cerebrospinal fluid concentrations of glycine, but also can not effectively improve the clinical symptoms. The use of tranquillizers (such as Valium), methionine (methionine), Antidote (Leucovorin), or choleretic agents (Choline), such as drugs, while only a slight improvement in clinical symptoms or even no response.

Recent report indicates that there is also another treatment to try, in accordance with glycine are excitatory nerve agents and the use of the hypothesis of NMDA antagonists (such as chlorine Ketamine Security ketone) or blockers (such as Dextromethorphan). Have reported that by a 7-month high with the non-ketone glycine Hyperlipemia baby every day oral non-barbiturate agent of general anesthesia such as chlorine-an-one (Ketamine), every day per kilogram of body weight 8 grams of ketamine four times using it, can improve the part of the neurological symptoms and brain waves. Hamosh et al have combined antitussive agents (dextromethorphan), and NMDA pipeline (NMDA channel) blocking agents and high doses of sodium Benzoin (sodium benzoate) therapy HKH cases, such treatment will be carried out one year after the results were published out. In this case sodium Benzoin (sodium benzoate) initial treatment dose of 500 mg per kg every day (500mg/kg/day), from the fifth day after birth, they start taking it to the first 8 days of each dose was increased to day 750 mg per kilogram. The first 12 days then add the antitussive agents, antitussive agents (dextromethorphan) starting dose was 7.5 mg per kg every day (7.5mg/kg/day). The case was heard up to 12 months of age except values development (developmental quotient) than the slow addition of 60, the physical examination and showed normal growth. The report can be found from the early use of NMDA receptor (NMDA receptor) antagonist, or blocker, may help to improve the patient's brain injury NKH.

Genetic

Non-keto high glycine hyperlipidemia are autosomal recessive inheritance, the next child the chance of recurrence is 25%. Its prevalence has not been one really knows. At the northern part of Finland, it is estimated that the prevalence for each of around 10,002 people in there is a (1:12000). In Taiwan, the prevalence is unknown, only a small number of cases have been discovered.